Association of autoimmune pancreatitis with Raghib syndrome

Key Clinical Message Autoimmune pancreatitis (AIP) is a form of chronic pancreatitis scarcely found in children. Raghib syndrome is a rare congenital heart defect known as persistent left superior vena cava (LSVC) draining into the left atrium. Total signs of Raghib syndrome in AIP case accompanied by an IgG4‐related disease were described. Abstract Autoimmune pancreatitis (AIP) is a form of chronic pancreatitis scarcely found in children. Raghib syndrome is a rare congenital heart defect known as persistent left superior vena cava (LSVC) draining into the left atrium. Here, we describe Raghib syndrome in AIP case accompanied by an IgG4‐related disease (AIP/IgG4RD). A 13‐year‐old boy presented with a 3‐month history of fever and abdominal pain. The laboratory findings showed SGOT and SGPT, ALP was increased, while amylase and γ‐GT were normal. Immunoglobulins were normal, except for IgG. Endosonography, spiral CT of the abdomen, and cholangiopancreatography showed an enlargement of the pancreas. Contrast echocardiography discovered opacification of the coronary sinus and left atrium. Transesophageal echocardiography for LSVC revealed a dilatation in the coronary sinus, indicating persistent LSVC. Following the injection of agitated saline into the left antecubital vein, bubbles entered both left and right atria in LSVC. It is reasonable to exclude some of these rare disorders as Raghib syndrome, in cases that will be started on medications like corticosteroids, which increases the susceptibility to thromboembolic events.

pseudotumor. 1 It has been scarcely described in children. 2 From the clinical viewpoint, patients may complain of abdominal pain, jaundice, weight loss and may present obstructive patterns in liver function tests (LFT).There is usually diffuse enlargement of the pancreas in imaging with diffusely or segmentally narrowed pancreatic ducts. 3 new clinicopathologic concept of IgG4-related systemic disease (ISD) has been proposed by Kamisawa et al. 4 In fact, ISD is defined as a syndrome characterized by elevated serum IgG4 levels, prominent lymphoplasmacytic infiltrate with increased IgG4 + plasma cells, dense sclerosis storiform fibrosis, and obliterative phlebitis.The fibrosis correlated with ISD may corrupt and even partially kill the affected organ; however, inflammatory process typically responds to corticosteroid therapy. 3,5][8] Notably, the LSVC itself causes no hemodynamic trouble and is often diagnosed incidentally. 9There is an increased risk of paradoxical embolism with LSVC due to its association with interatrial septal defect, unroofed coronary sinus, or direct communication to the left atrium. 7t drains into the right atrium via an enlarged coronary sinus in approximately 90% of patients.On rare occasions, the persistent left SVC directly enters the left atrium, creates a right to left shunt, resulting in partial anomalous systemic venous return. 10The standard method for the diagnosis is echocardiography, either transthoracic or transoesophageal.The most frequent echocardiographic feature of persistent LSVC (PSLVC) is a dilated coronary sinus and should hint the echocardiographer to look for a PLSVC.The diagnosis is then confirmed by contrast echocardiography.After excited saline injection into a leftsided brachial vein, bubble contrast seems in the coronary sinus before appearing in the right atrium and ventricle.Raghib syndrome is a sporadic congenital heart defect characterized by persistent left superior vena cava (LSVC) draining into the left atrium and the absence of the coronary sinus. 10Here, we reported an uncommon finding of Raghib syndrome in a case with AIP accompanied by an IgG4-related disease (AIP/IgG4RD).

| CASE PRESENTATION
Our patient is a 13-year-old boy who presented with a 3-month history of fever, anorexia, mild icterus, pale conjunctiva, myalgia, arthralgia, weight-bearing pain, headache, epigastric and right upper quadrant pain.The abdomen was soft without tenderness or organomegaly.In physical examination, there was no detectable lymphadenopathy.He had a mild fever (37.8°C) and complained about a 5-kg loss of weight during this period.
Immunoglobulins (IgA, IgG, and IgM) levels were normal, except for IgG (188 IU/mL).Sterile pyuria (WBC: 40-45 and RBC: 2-3) was also detected.Abdominal sonography revealed the enlargement of the left liver lobe, pancreas, and lymph nodes in the mesenteric and paraaortic areas.It increased corticomedullary differentiation in both kidneys (Head: 30 mm, body: 10 mm, and tail: 12 mm).Dimercaptosuccinic acid (DMSA) showed a scar in the lower portion of the right kidney.The wholebody scan was normal.Endosonography and spiral CT of the abdomen showed the prominence of head of pancreas and periceliac artery soft tissue infiltration, and enlarged kidneys.MR Cholangiopancreatography revealed an enlargement of the pancreas, standard caliber and length of common bile duct, and cystic duct, but a narrowed pancreatic duct with non-homogenous internal structure.In addition, liver biopsy showed chronic hepatitis.Bone marrow aspiration also revealed erythroid hyperplasia and dyserythropoietic changes.
A thorough history was taken to assess probable cardiac complications of an inflammatory process, and the physical examination was followed by performing electrocardiography and echocardiography.Transthoracic echocardiography revealed mild mitral valve prolapse without verrucae and mild MR.He was also detected to have unexplained grossly dilated coronary sinus (CS).Since we must follow the existence of persistent LSVC in every person with dilated coronary sinus, it was observed as a retrograde flow from the upper neck toward coronary sinus in suprasternal view echocardiography.Subsequently, contrast echocardiography from both arms discovered opacification of the CS and left atrium before the right atrium, which raised the suspicion of an unroofed CS.To confirm this, transesophageal echocardiography (TEE) was performed.TEE with contrast revealed both RSVS and LSVC.Right SVC drainage was normal.Injecting agitated saline into the left antecubital vein, LSVC showed bubble entrance into the left and right atria.

| DISCUSSION
Autoimmune pancreatitis (AIP) is a rare and newly recognized form of chronic pancreatitis, which can be misleadingly diagnosed as pancreatic cancer. 11This condition was first described in adults and is rarely reported in children. 3 AIP is histologically characterized by diffuse lymphoplasmacytic infiltration, obliterative phlebitis, and interstitial fibrosis. 12Numerous affected patients have hypergammaglobulinemia and increased serum levels of IgG, particularly IgG4. 13ecently, Mayo Clinic introduced several criteria for diagnosing AIP, summarized by the mnemonic HI-SORt, these criteria include five cardinal features of AIP in histology, imaging, serology, other organ involvements, and response to corticosteroid therapy. 14,15IP is infrequently associated with other autoimmune disorders such as Sjogren syndrome, idiopathic retroperitoneal fibrosis, and inflammatory bowel disease (IBD).Extrapancreatic manifestations include sclerosing cholangitis, renal mass or nephritis, retroperitoneal fibrosis, and submandibular masses. 16aghib syndrome is an uncommon congenital heart defect described by persistent left superior vena cava (LSVC) draining into the left atrium and the absence of the coronary sinus. 17,18o the best of our knowledge, the occurrence of Raghib syndrome or unroofed LSVC in a case with AIP has not been reported yet.We detected a dilated coronary sinus in echocardiography guided to find the PLSVC.In our patient, PLSVC was confirmed to have drainage to the left atrium as well.
Moreover, PLSVC is asymptomatic, and an incidental finding is often discovered incidentally during cardiovascular imaging or surgery, left subclavian vein cannulation, or device implantation. 19n this case, an echocardiographic examination revealed dilated coronary sinus that raised the suspicion of LSVC.Therefore, simple agitated saline bolus injections into the left antecubital veins (contrast echocardiography) were performed.Scanning healthy individuals in four-chamber view reveals the saline contrast, administered thorough left upper extremity vein, first in the right atrium.In this regard, the contrast will first appear in the dilated coronary sinus then in the left atrium if there is PSVC drainage to the LA.
In a retrospective study, the patients who underwent either pacemaker or ICD implantation PLSVC were estimated at 0.41% of the general population, emphasizing critical clinical implications and difficulties during central venous access, cardiothoracic surgeries, and pacemaker implantation.When the left upper extremity is used for accessing, serious complications such as arrhythmia, tamponade, and coronary sinus thrombosis may occur due to manipulating the catheter in the CS. 20urthermore, a higher incidence of cardiac arrhythmias and conductive defects has been reported in patients with PLSVC.This may be secondary to stretching and fibrosis of the atrioventricular node or His bundle by the dilated CS or associated sinus node dysfunction. 3ur patient was prone to infection or GI bleeding because of his underlying disorder and decreased immunocompetence.There was a risk of being manipulated with repeated IV catheter insertions and its mentioned complications.In addition, any dysrhythmia might be attributed to an underlying autoimmune disorder instead of an underlying neglected cardiac anomaly.Besides, the dilated CS has been known even to produce left ventricular inflow obstruction and heart failure. 21ince one of the most important medications used in AIP is corticosteroid therapy, which can lead to thromboembolic events itself, the risk of CVA in our patient could be estimated higher than usual.It is reasonable to exclude some of these rare disorders as Raghib syndrome, in cases that will initiate medications as corticosteroid therapies, which raise the probability of thromboembolic events.Lymphoplasmacytic aortitis has been previously described as an IgG4-related disease. 22In our case, the aortic root was intact, and dimensions and elasticity had average values.
Most common congenital defects associated with combined great venous malformation included various types of atrial septal defects, endocardial cushion defects, and tetralogy of Fallot. 23In this case, the initial structural and functional disorders detected were mitral valve prolapse and mild mitral regurgitation, respectively.
The principal differential diagnosis for this finding would be indolent rheumatic mitral involvement, which could be differentiated from each other by WHO recommendations. 24According to these criteria, rheumatic involvement was excluded with a high probability.
Prednisolone was started for the patient, and he was a candidate for elective corrective surgery of unroofed LSVC.To the best of our knowledge, these two entities never have been reported to exist in the same patient.This infrequent association has not been reported yet, and there is no data that Raghib syndrome may have been the cause of autoimmunity.This issue must be followed up.

| CONCLUSION
One of the most critical complications of PLSVC is paradoxical emboli.Medications as corticosteroids can lead to thromboembolic events themselves.It is reasonable to exclude some of these rare disorders as Raghib syndrome in cases who are going to be started on medications as corticosteroids which increases susceptibility to thromboembolic events.Particular attention should be paid to anatomical configuration such as dilated coronary sinus during echocardiography awareness about these conditions and comorbidities are essential to avoid complications.